This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Allen, R. D.
Right arrow Articles by Siu, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Allen, R. D., III
Right arrow Articles by Siu, G.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, May 2001, p. 3071-3082, Vol. 21, No. 9
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.9.3071-3082.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Negative Regulation of CD4 Gene Expression by a HES-1-c-Myb Complex

Robert D. Allen III,dagger Han K. Kim, Sophia D. Sarafova,Dagger and Gerald Siu*

Department of Microbiology, Columbia University, College of Physicians and Surgeons, New York, New York 10032

Received 24 March 2000/Returned for modification 5 June 2000/Accepted 5 February 2001

Expression of the CD4 gene is tightly controlled throughout thymopoiesis. The downregulation of CD4 gene expression in CD4- CD8- and CD4- CD8+ T lymphocytes is controlled by a transcriptional silencer located in the first intron of the CD4 locus. Here, we determine that the c-Myb transcription factor binds to a functional site in the CD4 silencer. As c-Myb is also required for CD4 promoter function, these data indicate that depending on the context, c-Myb plays both positive and negative roles in the control of CD4 gene expression. Interestingly, a second CD4 silencer-binding factor, HES-1, binds to c-Myb in vivo and induces it to become a transcriptional repressor. We propose that the recruitment of HES-1 and c-Myb to the silencer leads to the formation of a multifactor complex that induces silencer function and repression of CD4 gene expression.

* Corresponding author. Mailing address: Department of Microbiology, Columbia University, College of Physicians and Surgeons, 701 West 168th St., New York, NY 10032. Phone: (212) 305-2743. Fax: (212) 305-8013. E-mail: siu{at}cusiu3.cpmc.columbia.edu.

dagger Present address: Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110.

Dagger Present address: Experimental Immunology Branch, National Cancer Institute, Bethesda, MD 20892-1360.

Molecular and Cellular Biology, May 2001, p. 3071-3082, Vol. 21, No. 9
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.9.3071-3082.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Kathrein, K. L., Chari, S., Winandy, S. (2008). Ikaros Directly Represses the Notch Target Gene Hes1 in a Leukemia T Cell Line: IMPLICATIONS FOR CD4 REGULATION. J. Biol. Chem. 283: 10476-10484 [Abstract] [Full Text]  
  • Yu, M., Wan, M., Zhang, J., Wu, J., Khatri, R., Chi, T. (2008). Nucleoprotein structure of the CD4 locus: Implications for the mechanisms underlying CD4 regulation during T cell development. Proc. Natl. Acad. Sci. USA 105: 3873-3878 [Abstract] [Full Text]  
  • Fischer, A., Gessler, M. (2007). Delta Notch and then? Protein interactions and proposed modes of repression by Hes and Hey bHLH factors. Nucleic Acids Res 35: 4583-4596 [Abstract] [Full Text]  
  • Mertz, J. A., Kobayashi, R., Dudley, J. P. (2007). ALY Is a Common Coactivator of RUNX1 and c-Myb on the Type B Leukemogenic Virus Enhancer. J. Virol. 81: 3503-3513 [Abstract] [Full Text]  
  • Sinkora, M., Sinkorova, J., Cimburek, Z., Holtmeier, W. (2007). Two Groups of Porcine TCR{gamma}{delta}+ Thymocytes Behave and Diverge Differently. J. Immunol. 178: 711-719 [Abstract] [Full Text]  
  • Shen, Q., Christakos, S. (2005). The Vitamin D Receptor, Runx2, and the Notch Signaling Pathway Cooperate in the Transcriptional Regulation of Osteopontin. J. Biol. Chem. 280: 40589-40598 [Abstract] [Full Text]  
  • Grueter, B., Petter, M., Egawa, T., Laule-Kilian, K., Aldrian, C. J., Wuerch, A., Ludwig, Y., Fukuyama, H., Wardemann, H., Waldschuetz, R., Moroy, T., Taniuchi, I., Steimle, V., Littman, D. R., Ehlers, M. (2005). Runx3 Regulates Integrin {alpha}E/CD103 and CD4 Expression during Development of CD4-/CD8+ T Cells. J. Immunol. 175: 1694-1705 [Abstract] [Full Text]  
  • Murata, K., Hattori, M., Hirai, N., Shinozuka, Y., Hirata, H., Kageyama, R., Sakai, T., Minato, N. (2005). Hes1 Directly Controls Cell Proliferation through the Transcriptional Repression of p27Kip1. Mol. Cell. Biol. 25: 4262-4271 [Abstract] [Full Text]  
  • Nomura, T., Tanikawa, J., Akimaru, H., Kanei-Ishii, C., Ichikawa-Iwata, E., Khan, M. M., Ito, H., Ishii, S. (2004). Oncogenic Activation of c-Myb Correlates with a Loss of Negative Regulation by TIF1{beta} and Ski. J. Biol. Chem. 279: 16715-16726 [Abstract] [Full Text]  
  • Telfer, J. C., Hedblom, E. E., Anderson, M. K., Laurent, M. N., Rothenberg, E. V. (2004). Localization of the Domains in Runx Transcription Factors Required for the Repression of CD4 in Thymocytes. J. Immunol. 172: 4359-4370 [Abstract] [Full Text]  
  • Ehlers, M., Laule-Kilian, K., Petter, M., Aldrian, C. J., Grueter, B., Wurch, A., Yoshida, N., Watanabe, T., Satake, M., Steimle, V. (2003). Morpholino Antisense Oligonucleotide-Mediated Gene Knockdown During Thymocyte Development Reveals Role for Runx3 Transcription Factor in CD4 Silencing During Development of CD4-/CD8+ Thymocytes. J. Immunol. 171: 3594-3604 [Abstract] [Full Text]  
  • Yan, B., Raben, N., Plotz, P. (2002). The Human Acid alpha -Glucosidase Gene Is a Novel Target of the Notch-1/Hes-1 Signaling Pathway. J. Biol. Chem. 277: 29760-29764 [Abstract] [Full Text]  
  • Reizis, B., Leder, P. (2001). The Upstream Enhancer Is Necessary and Sufficient for the Expression of the Pre-T Cell Receptor {alpha} Gene in Immature T Lymphocytes. JEM 194: 979-990 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»